Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis
Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis
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DOI：
10.1016/j.cardiores.2007.02.028
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发表时间：
2007-06-01
影响因子：
10.8
通讯作者：
Shimpo, Hideto
中科院分区：
文献类型：
--
作者：
Sawada, Yasuhiro;Onoda, Koji;Shimpo, Hideto
目的：腱蛋白-C（Tenascin-C）是一种细胞外基质糖蛋白，被认为在动脉旁路移植物的新内膜增生中发挥重要作用。在本研究中，使用生腱蛋白-C转基因小鼠检查生腱蛋白-C对游离动脉移植物的新内膜增生的直接贡献以及生腱蛋白-C产生细胞的起源。方法和结果：在小鼠中进行腹主动脉至颈动脉间置移植。当将野生型小鼠的移植物移植到野生型小鼠时，在第14天和第28天在移植物中观察到新内膜增生。免疫组织化学染色显示移植物的中膜和新内膜中生腱蛋白-C强表达。当将生腱蛋白 C 缺陷小鼠的移植物移植到生腱蛋白 C 缺陷小鼠时，新内膜增生要少得多。在移植到野生型小鼠的生腱蛋白-C 缺陷移植物中，仅在新内膜中观察到生腱蛋白-C 沉积。在相反的组合中，在中膜和新内膜中看到沉积。使用同样表达生腱蛋白-C 和 LacZ 的杂合小鼠分析生腱蛋白-C 产生细胞的来源。虽然 LacZ 阳性细胞仅在野生型移植到突变型小鼠的动脉移植物的新内膜中可见，但在突变型小鼠移植到野生型小鼠的移植物的新内膜和中膜中均检测到阳性细胞。 结论：我们提供了直接证据，表明生腱蛋白-C 是游离动脉移植物新内膜增生的关键分子，并且生腱蛋白-C 产生细胞均来自供体移植物和受体。 (C) 2007 年欧洲心脏病学会。由 Elsevier B.V. 出版。保留所有权利。
Objective: Tenascin-C, an extracellular matrix glycoprotein, is thought to play an important role in neointimal hyperplasia of artery bypass grafts. In this study, the direct contribution of tenascin-C to neointimal hyperplasia of free artery grafts and the origin of tenascin-C-producing cells were examined using tenascin-C transgenic mice.Methods and results: Abdominal aorta-to-carotid artery interposition grafting was performed in mice. When grafts from wild-type mice were transplanted to wild-type, neointimal hyperplasia was observed in the grafts at days 14 and 28. Immumohistochemical staining showed strong expression of tenascin-C in the media and neointima of the grafts. Much less neointimal hyperplasia was seen when grafts from tenascin-C-deficient mice were transplanted to tenascin-C-deficient mice. In tenascin-C-deficient grafts transplanted to wild-type mice, tenascin-C deposition was observed only in the neointima. In the reverse combination, deposition was seen in the media and neointima. The source of the tenascin-C-producing cells was analyzed using heterozygous mice that identically express both tenascin-C and LacZ. While LacZ-positive cells were seen only in the neointima of artery grafts from wild-type transplanted to mutant mice, positive cells were detected in both the neointima and media in grafts from mutant to wild-type mice.Conclusions: We presented direct evidence that tenascin-C is a crucial molecule in neointimal hyperplasia in free artery grafts, and that tenascin-C-producing cells are derived from both donor grafts and recipients. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.